Mayo Clinic scientists develop new combination therapy for advanced cancers

Researchers at the Mayo Clinic have figured out a new way to beat metastatic cancer in a mouse model using a combination therapy that targets the immune system. The therapy is now being pursued in clinical trials and may hold promise for patients with advanced cancers such as pancreas, breast, colorectal and melanoma.

The co-authors of the study, Peter Cohen and Sandra Gendler, published their findings in the journal Oncotarget.

“We tested Toll-like receptor (TLR) agonists--drugs that mimic invasive bacteria--as a strategy to trick the immune system into attacking cancer as if it were a life-threatening infection,” said Cohen in a statement. They tested TLR agonists with 10 different chemotherapy agents that are also known to enhance immunotherapy.

Using a combination of TLR agonists and chemotherapy agents, they found cyclophosphamide to be the most effectively in combination with any of the TLR agonists. To arrive at this finding they tried the drug combinations in two mouse models that recapitulate highly aggressive cancers: breast and pancreatic cancer.

They saw regression of the cancers within two cycles of treatment, and if the mice received five additional cycles of treatment the cancer did not recur. The TLR agonist/cyclophosphamide was the only chemotherapy combination to result in permanent cancer eradication. The researchers say that the combination therapy was very well tolerated, and in fact, more so than if either drug were given individually.

The researchers also say the combination drug didn’t need to be injected into the tumor directly and was effective in widespread metastases over and above the primary tumor site. An added benefit of the drug combination was the finding that monocytes (a type of white blood cell) were also activated upon injection.

“It appears very likely that each round of treatment stimulates the bone marrow to churn out freshly activated monocytes, which distribute throughout the body, spare normal cells, and find and kill cancer cells,” said Gendler.

They’re currently pursuing an FDA-approved clinical trial for the use of cyclophosphamide and the TLR agonist motolimod, in patients with a range of advanced cancers.

- here’s the release

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